Which chemotherapy drug causes the worst 'chemobrain'?

Patients who undergo chemotherapy for breast cancer often report a long-lasting drop in cognitive functioning. New research investigates which drug causes the worst cognitive deficits.

Chemobrain is a common complaint among breast cancer survivors.

This well-known effect, dubbed "chemobrain," is a significant negative factor in the lives of post-breast cancer patients.

Radiotherapy already has proven negative effects on cognitive performance, and it is becoming ever clearer that chemotherapy has similar issues.

Patients report a general mental cloudiness during and after treatment.

Chemobrain has been studied in the past, but until now, the comparative effects of different drug regimens has not been studied.

Recent research published in JAMA Oncology compares the effects of anthracycline-based and nonanthracycline-based treatment on cognitive functioning and brain connectivity after chemotherapy.

This is the first time two courses of treatment have been pitted against each other regarding chemobrain outcomes.

What is chemobrain?

Chemobrain is reported to significantly reduce the quality of life in women who have undergone chemotherapy for breast cancer and survived to tell the tale.

Neuroimaging seems to infer that chemotherapy causes a diffuse, widespread injury to the brain and possibly increases sensitivity to future neurodegeneration.

Reported symptoms of chemobrain can include:

Forgetting things that would normally come to mind with ease

Loss of focus and decline in attention span

Difficulty in multitasking

Forgetting common words, dates and events

Taking longer to complete tasks, easily distracted.

Previous research has demonstrated that some of these cognitive losses might be due, in part, to changes in the default mode network.

The default mode network includes the precuneus, cingulate, medial frontal, middle temporal and lateral parietal regions of the brain, plus the hippocampus. This network is believed to be involved in implicit learning, monitoring and the allocation of neural resources to various cognitive processes.

Anthracycline-based group performed worse on verbal memory tasks

The current study was headed up by Shelli R. Kesler, PhD, of the University of Texas MD Anderson Cancer Center in Houston, and Dr. Douglas W. Blayney, of the Stanford University School of Medicine in California.

The research utilized retrospective data from 62 breast cancer survivors who finished treatment at least 2 years earlier. Of this group, 20 had been treated with anthracycline-based chemotherapy, 19 had been given nonanthracycline-based drugs and the remaining 23 had not received any chemotherapy.

The authors recognize that the sample group is small, but results gleaned from this study can be used as the impetus to conduct more research.

The team found that the women in the anthracycline-based group performed significantly worse on verbal memory tasks and showed less lower left precuneus connectivity.

Also, patient self-reported outcomes of cognitive dysfunction and psychological distress were higher in both chemotherapy groups, compared with the non-chemotherapy group.

The precuneus and its neighbors

Although a relatively unstudied area of the brain, the precuneus' role appears to be an important one. The precuneus and surrounding areas have the highest resting metabolic rates in the brain; a sure sign that they have a lot of work to do.

It is thought to play a role in a number of integrated tasks, including visuospatial imagery and the retrieval of episodic (autobiographical) memories.

Connections between the precuneus and the frontal, hippocampal and lateral parietal regions were found to be lacking in the anthracycline-based group's brains. This lack of linkage is thought to disrupt the efficiency of information processing and lessen dynamic responses in cognitive tasks.

As for the mechanisms at work in degenerating connectivity in these specific brain regions, that is up for debate. One theory involves cytokines. Anthracycline-based chemotherapy has been found to release more proinflammatory cytokines, causing increased neuroinflammation that may be to blame.

Another avenue of interest might be the effects of oxidative stress on the brain. Chemotherapy has been found to produce reactive oxygen species and, at the same time, reduce the patient's ability to react and clear the destructive agents. This could lead to direct damage of the neurons.

The authors conclude:

"These results should be considered preliminary given the study limitations of small sample size and retrospective, cross-sectional design.

Larger, prospective studies are needed that include pretreatment and post-treatment assessments so that patients' individual cognitive and neurobiologic trajectories can be evaluated with respect to potential anthracycline-related neurotoxic effects."

Chemotherapy, its effectiveness and its consequences are rightfully under constant scrutiny. With time, no doubt, the chemobrain phenomenon will become well understood and preventable.

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